Survey Sequencing and Comparative Analysis of the Elephant Shark (Callorhinchus milii) Genome

Abstract

Owing to their phylogenetic position, cartilaginous fishes (sharks, rays, skates, and chimaeras) provide a critical reference for our understanding of vertebrate genome evolution. The relatively small genome of the elephant shark, Callorhinchus milii, a chimaera, makes it an attractive model cartilaginous fish genome for whole-genome sequencing and comparative analysis. Here, the authors describe survey sequencing (1.4× coverage) and comparative analysis of the elephant shark genome, one of the first cartilaginous fish genomes to be sequenced to this depth. Repetitive sequences, represented mainly by a novel family of short interspersed element–like and long interspersed element–like sequences, account for about 28% of the elephant shark genome. Fragments of approximately 15,000 elephant shark genes reveal specific examples of genes that have been lost differentially during the evolution of tetrapod and teleost fish lineages. Interestingly, the degree of conserved synteny and conserved sequences between the human and elephant shark genomes are higher than that between human and teleost fish genomes. Elephant shark contains putative four Hox clusters indicating that, unlike teleost fish genomes, the elephant shark genome has not experienced an additional whole-genome duplication. These findings underscore the importance of the elephant shark as a critical reference vertebrate genome for comparative analysis of the human and other vertebrate genomes. This study also demonstrates that a survey-sequencing approach can be applied productively for comparative analysis of distantly related vertebrate genomes. Cartilaginous fishes (sharks, rays, skates, and chimaeras) are the phylogenetically oldest group of living jawed vertebrates. They are also an important outgroup for understanding the evolution of bony vertebrates such as human and teleost fishes. We performed survey sequencing (1.4× coverage) of a chimaera, the elephant shark (Callorhinchus milii). The elephant shark genome, estimated to be about 910 Mb long, comprises about 28% repetitive elements. Comparative analysis of approximately 15,000 elephant shark gene fragments revealed examples of several ancient genes that have been lost differentially during the evolution of human and teleost fish lineages. Interestingly, the human and elephant shark genomes exhibit a higher degree of synteny and sequence conservation than human and teleost fish (zebrafish and fugu) genomes, even though humans are more closely related to teleost fishes than to the elephant shark. Unlike teleost fish genomes, the elephant shark genome does not seem to have experienced an additional round of whole-genome duplication. These findings underscore the importance of the elephant shark as a useful “model” cartilaginous fish genome for understanding vertebrate genome evolution.